[Long-term depression of excitatory synapses in the cortex and hippocampus]

The efficacy of excitatory synapses terminating on cortical and hippocampal pyramidal cells may be persistently depressed as well as potentiated. Homo-synaptic long-term depression (LTD) seems to be triggered by an entry of calcium into a post-synaptic cell less than that needed to initiate long-term potentiation (LTP). Theoretical work predicted, and experimental studies confirmed, that moderate elevations of calcium initiate LTD via a cascade of biochemical interactions involving calcium-dependent phosphatases. Genetically modified animals confirmed the prediction of a sliding threshold that defines the limit between LTD and LTP. While mechanisms for the initiation of LTD are quite well established, it remains unclear whether pre- or post-synaptic mechanisms, or both, are involved in its maintenance. A role for LTD in processes of learning and forgetting in the adult animal remains to be firmly established. It seems probable, however, that a persistent reduction in synaptic weight is a basic process used in the establishment and refinement of neuronal circuits during development.